A spheroid-forming conductive platform that electrochemically detects anticancer effects of curcumin in a multicellular brain cancer model

( Suhito Intan Rosalina ),김태형 한국공업화학회 2021 한국공업화학회 연구논문 초록집 Vol.2021 No.0

Rapid and sensitive electrochemical detection of anticancer effects of curcumin on human glioblastoma cells

Suhito, Intan Rosalina,Lee, Wanhee,Baek, Seungho,Lee, Donghyun,Min, Junhong,Kim, Tae-Hyung Elsevier 2019 Sensors and actuators. B Chemical Vol.288 No.-

<P><B>Abstract</B></P> <P>Curcumin, a hydrophobic polyphenol derived from the <I>Curcuma longa</I> plant, is known to affect various cellular activities such as cell cycle regulation, oncogene expression, apoptosis, and mutagenesis, and is thus considered a promising candidate for an anticancer drug. In this study, we report the development of a platform that is effective to evaluate the anticancer effects of curcumin on one of the most aggressive tumors, glioblastoma. To generate platforms that satisfy both rapid and sensitive detection of curcumin effects, the surface of transparent conductive electrodes was first modified with two different types of electrocatalytic materials, gold and silver nanoparticles, with different densities. Among the four different substrates fabricated, a high-density gold nanostructure film (HDGN) in combination with peptide modification was found to be the best in terms of measuring the electrochemical signals of human glioblastoma cells (U87MG). The electrical signals of U87MG cells (E<SUB>pc</SUB> = -0.05 V vs. Ag/AgCl), obtained from cyclic voltammetry, showed excellent linearity (R<SUP>2</SUP> = 0.99) within the range of 20,000–60,000 cells, and were thus demonstrated to be suitable for assessment of curcumin anticancer effects on U87MG cells. A clear curcumin toxicity on human glioblastoma was found with concentrations higher than 30 μM, which was consistent with the results obtained from cell counting kit-8 (CCK-8) assays. Remarkably, unlike the conventional colorimetric methods, the HDGN/peptide-modified platform was completely free from a possible signal interference from curcumin (absorbance: 425 nm). In addition, it enabled rapid (detection time < 3 min) and precise (limit of quantification: 9379 cells/chip) assessments of the potential toxicity of curcumin for cancer cells. Hence, we conclude that the developed platform is highly promising for use as a high-throughput screening tool for the discovery of new types of less toxic plant-derived natural anticancer drugs.</P> <P><B>Highlights</B></P> <P> <UL> <LI> An electrochemical biosensor was developed to evaluate the anticancer effects of curcumin. </LI> <LI> A high-density metal nanostructure with peptide modification was constructed as a platform. </LI> <LI> Both LOQ and detection time of the developed biosensor were superior to conventional colorimetric method. </LI> <LI> The developed platform was completely free from the signal interference from the drug. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Effects of two-dimensional materials on human mesenchymal stem cell behaviors

Suhito, Intan Rosalina,Han, Yoojoong,Kim, Da-Seul,Son, Hyungbin,Kim, Tae-Hyung Academic Press 2017 Biochemical and biophysical research communication Vol. No.

<P><B>Abstract</B></P> <P>Graphene, a typical two-dimensional (2D) material, is known to affect a variety of stem cell behaviors including adhesion, spreading, growth, and differentiation. Here, we report for the first time the effects of four different emerging 2D materials on human adipose-derived mesenchymal stem cells (hADMSCs). Graphene oxide (GO), molybdenum sulfide (MoS<SUB>2</SUB>), tungsten sulfide (WS<SUB>2</SUB>), and boron nitride (BN) were selected as model two-dimensional materials and were coated on cell-culture substrates by a drop-casting method. Acute toxicity was not observed with any of the four different 2D materials at a low concentration range (<5 μg/ml). Interestingly, the 2D material-modified substrates exhibited a higher cell adhesion, spreading, and proliferation when compared with a non-treated (NT) substrate. Remarkably, in the case of differentiation, the MoS<SUB>2</SUB>-, WS<SUB>2</SUB>-, and BN-modified substrates exhibited a better performance in terms of guiding the adipogenesis of hADMSCs when compared with both NT and GO-modified substrates, based on the mRNA expression level (qPCR) and amount of lipid droplets (ORO staining). In contrast, the osteogenesis was found to be most efficiently induced by the GO-coated substrate (50 μg/mL) among all 2D-material coated substrates. In summary, 2D materials could act as favorable sources for controlling the stem cell growth and differentiation, which might be highly advantageous in both biomedical research and therapy.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The toxicity of four different two-dimensional materials on hADMSCs was studied. </LI> <LI> All four different 2D materials enhanced the cell adhesion, spreading and proliferation. </LI> <LI> WS<SUB>2</SUB>-, MoS<SUB>2</SUB>-, and BN-coated substrates enhanced the adipogenesis of hADMSCs. </LI> <LI> GO showed the best performance for guiding the osteogenesis of hADMSCs. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

<i>In situ</i> label-free monitoring of human adipose-derived mesenchymal stem cell differentiation into multiple lineages

Suhito, Intan Rosalina,Han, Yoojoong,Min, Junhong,Son, Hyungbin,Kim, Tae-Hyung Elsevier 2018 Biomaterials Vol.154 No.-

<P><B>Abstract</B></P> <P>Precise characterizations of stem cell differentiation into specific lineages, especially in non-destructive and non-invasive manner, are extremely important for generating patient-specific cells without mass loss of differentiated cells. Here, we report a new method capable of <I>in situ</I> label-free quantification of stem cell differentiation into multiple lineages, even at a single cell level. The human adipose-derived mesenchymal stem cells (hADMSCs) were first differentiated into two different types of cells (osteoblasts and adipocytes) and these differentiated cells were then intensively analyzed by micro-Raman spectroscopy. Interestingly, the Raman peaks assigned to lipid droplets and hydroxyapatite were found to be highly specific to the adipocyte (fat cell) and osteoblast (bone cell) and were thus found to be useful for generating label-free single cell Raman images in combination with CH<SUB>3</SUB> (2935 cm<SUP>−1</SUP>) peaks for visualizing cell shape. Remarkably, based on these Raman images, we found that the osteogenesis of hADMSCs could be determined and quantified after 9 days of differentiation, which is a week earlier than with the typical alizarin red staining method. In the case of adipogenesis, the increase of lipid droplets in the cytoplasm at the single cell level could be clearly visualized and detected during the entire period of adipogenesis, which is impossible using any other currently available methods such as Oil Red O and immunostaining. Hence, the new method reported in this study is highly promising as an analytical tool for precise <I>in-situ</I> monitoring of stem cell differentiation, and could facilitate the use of stem cell-based materials for the regenerative therapies.</P>

Raman Spectroscopy-based 3D Analysis of Odontogenic Differentiation of Human Dental Pulp Stem-cell Spheroids

Huijung KIM,Yoojoong HAN,Intan Rosalina SUHITO,Hyungbin SON,Hyung-Ryong KIM,Tae-Hyung KIM 한국생물공학회 2021 한국생물공학회 학술대회 Vol.2021 No.4

Two-dimensional material-based bionano platforms to control mesenchymal stem cell differentiation

Ee-Seul Kang,Da-Seul Kim,Intan Rosalina Suhito,Wanhee Lee,Inbeom Song,Tae-HyungKim 한국생체재료학회 2018 생체재료학회지 Vol.22 No.2

Background: In the past decade, stem cells, with their ability to differentiate into various types of cells, have been proven to be resourceful in regenerative medicine and tissue engineering. Despite the ability to repair damaged parts of organs and tissues, the use of stem cells still entails several limitations, such as low differentiation efficiency and difficulties in guiding differentiation. To address these limitations, nanotechnology approaches have been recently implemented in stem cell research. It has been discovered that stem cells, in combination with carbon-based functional materials, show enhanced regenerative performances in varying biophysical conditions. In particular, several studies have reported solutions to the conventional quandaries in biomedical engineering, using synergetic effects of nanohybrid materials, as well as further development of technologies to recover from diverse health conditions such as bone fracture and strokes. Main text: In this review, we discuss several prior studies regarding the application of various nanomaterials in controlling the behavior of stem cells. We focus on the potential of different types of nanomaterials, such as two-dimensional materials, gold nanoparticles, and three-dimensional nanohybrid composites, to control the differentiation of human mesenchymal stem cells (hMSCs). These materials have been found to affect stem cell functions via the adsorption of growth/differentiation factors on the surfaces of nanomaterials and the activation of signaling pathways that are mostly related to cell adhesion and differentiation (e.g., FAK, Smad, Erk, and Wnt). Conclusion: Controlling stem cell differentiation using biophysical factors, especially the use of nanohybrid materials to functionalize underlying substrates wherein the cells attach and grow, is a promising strategy to achieve cells of interest in a highly efficient manner. We hope that this review will facilitate the use of other types of newly discovered and/or synthesized nanomaterials (e.g., metal transition dichalcogenides, non-toxic quantum dots, and metal oxide frameworks) for stem cell-based regenerative therapies.